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MAGE-C1/CT7 spontaneously triggers a CD4+ T-cell response in multiple myeloma patients

Leukemia volume 27, pages 1767–1769 (2013)Cite this article

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Multiple myeloma (MM), a B-cell malignancy with accumulation of clonal, malignant plasma cells in the bone marrow, is the second most common haematological malignancy affecting over 20 000 patients each year in the United States.1 Although, allogeneic bone marrow transplantation is still performed at the expense of a significant treatment-related toxicity, the graft-versus-myeloma effect has demonstrated that MM cells can be eliminated by effector T cells, and moreover that this results in higher remission rates and even cures.2 By targeting antigens that are exclusively expressed by MM cells, the efficiency and safety of myeloma-specific immunotherapy can be drastically improved.3 Among the currently known tumour antigens, cancer-testis (CT) antigens represent one of the most relevant groups for the development of cancer immunotherapy because of their restricted expression in germ line and cancer tissues and their broad immunogenicity.4 Naturally occurring immune responses against CT antigens, that is, NY-ESO-1 and MAGE-A family of antigens have been previously described in MM patients.5 These responses were found frequently and often correlated with disease burden.

From the three patients with CT7-specific T-cell response, we could see that at the time of blood collection, patient ZH-590 had active disease (initial Stage III based on International Staging System (ISS) and III on Durie Salmon staging system (DSS)), patient ZH-259 had a stable disease with partial remission (initial stage I on ISS and III on DSS) and patient ZH-683 had progressive disease (initial stage I on ISS and III on DSS). Previously published report found naturally occurring MAGE-A-specific CD4+ T-cell response predominantly in monoclonal gammopathy of undetermined significance (MGUS) patients.14 One reason for this discrepancy could be that CT7 is prominently expressed in later stages of MM while MAGE-A is expressed consistently throughout MGUS and MM.7 The unavailability of peripheral blood samples from MGUS patients precludes any further conclusions.

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Acknowledgements

We thank the following associations for support: the Cancer Research Institute/Ludwig Institute for Cancer Research/Cancer Vaccine Collaborative/Atlantic Philantropies, the Terry Fox Foundation, the Hanne Liebermann Foundation, the Zürcher Krebsliga, and the Hartmann Müller Foundation. We thank JM Tiercy from University Hospital Geneva, Switzerland for kind help with HLA typing.

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  1. N Nuber

    Present address: 4Present address; Department of Biomedicine, University of Basel, Switzerland.,

  2. N Nuber and A Curioni-Fontecedro: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, University Hospital Zurich, Zurich, Switzerland

    N Nuber, A Curioni-Fontecedro, S R Dannenmann, C Matter, A Knuth & M van den Broek

  2. Department of Oncology and Hematology and Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    L von Boehmer & D Atanackovic

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Nuber, N., Curioni-Fontecedro, A., Dannenmann, S. et al. MAGE-C1/CT7 spontaneously triggers a CD4+ T-cell response in multiple myeloma patients. Leukemia 27, 1767–1769 (2013). https://doi.org/10.1038/leu.2013.31

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